A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen.
A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen.
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DOI：
10.1371/journal.pone.0009188
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发表时间：
2010-02-12
期刊：
影响因子：
3.7
通讯作者：
Campisi J
中科院分区：
文献类型：
--
作者：
Coppé JP;Patil CK;Rodier F;Krtolica A;Beauséjour CM;Parrinello S;Hodgson JG;Chin K;Desprez PY;Campisi J
细胞衰老会在致癌刺激下不可逆地阻止细胞增殖。人类细胞会形成一种衰老相关分泌表型（SASP），它会增加细胞因子及其他改变邻近细胞行为的因子的分泌。我们在此表明，在标准培养条件（20%氧气）下反复传代后停止生长的“衰老”小鼠成纤维细胞不会表达类似人类的SASP，并且在其他方面与同样培养的人类细胞不同。然而，当在生理（3%）氧气环境中培养并通过辐射诱导衰老时，小鼠细胞与人类细胞更为相似，包括会表达一种强烈的SASP。我们描述了人类和小鼠SASP的两个新方面。首先，两种物种的细胞都上调了几种基质金属蛋白酶的表达和分泌，这些蛋白酶构成了一个保守的基因组簇。其次，对于这两个物种，促进癌前上皮细胞生长的能力主要归因于保守的SASP因子CXCL - 1/KC/GRO -α。此外，在3%氧气（而非20%氧气）环境中衰老的小鼠成纤维细胞在小鼠异种移植中促进了上皮肿瘤发生。我们的研究结果强调了小鼠和人类在氧气敏感性方面的关键差异，确定了利用小鼠细胞模拟人类细胞衰老的条件，并揭示了SASP的新的保守特征。
Cellular senescence irreversibly arrests cell proliferation in response to oncogenic stimuli. Human cells develop a senescence-associated secretory phenotype (SASP), which increases the secretion of cytokines and other factors that alter the behavior of neighboring cells. We show here that “senescent” mouse fibroblasts, which arrested growth after repeated passage under standard culture conditions (20% oxygen), do not express a human-like SASP, and differ from similarly cultured human cells in other respects. However, when cultured in physiological (3%) oxygen and induced to senesce by radiation, mouse cells more closely resemble human cells, including expression of a robust SASP. We describe two new aspects of the human and mouse SASPs. First, cells from both species upregulated the expression and secretion of several matrix metalloproteinases, which comprise a conserved genomic cluster. Second, for both species, the ability to promote the growth of premalignant epithelial cells was due primarily to the conserved SASP factor CXCL-1/KC/GRO-α. Further, mouse fibroblasts made senescent in 3%, but not 20%, oxygen promoted epithelial tumorigenesis in mouse xenographs. Our findings underscore critical mouse-human differences in oxygen sensitivity, identify conditions to use mouse cells to model human cellular senescence, and reveal novel conserved features of the SASP.
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影响因子：
11.2
作者：
Bavik, C;Coleman, I;Nelson, PS
通讯作者：
Nelson, PS
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
DOI：
10.1002/cyto.10149
发表时间：
2002-10-01
期刊：
CYTOMETRY
影响因子：
--
作者：
Krtolica, A;de Solorzano, CO;Campisi, J
通讯作者：
Campisi, J
DOI：
10.1073/pnas.211053698
发表时间：
2001-10-09
影响因子：
11.1
作者：
Krtolica, A;Parrinello, S;Campisi, J
通讯作者：
Campisi, J